title: Protein spherulites for sustained release of interferon: preparation, characterization and in vivo evaluation.
abstract: This study develops protein spherulite, a new form of protein aggregation, for sustained-release applications of recombinant human interferon α-2b (rhIFN). rhIFN spherulites were prepared with different pH solutions with different kinds and concentrations of zinc salts at various incubation temperatures. rhIFN spherulites produced under different systems were of different morphology properties and in vitro release characters. Size-exclusion high-performance liquid chromatography analysis has shown that no protein aggregates were generated during spherulite formation, and cytopathic inhibition assay has demonstrated that the spherulitic rhIFN well maintained its structure and antiviral activity. In vivo studies showed that rhIFN spherulites provided a significantly prolonged pharmacokinetics profile profile as compared with the soluble rhIFN formulation, and the relative bioavailability based on serum rhIFN levels was about 170%. The work described here demonstrates the possibility of protein spherulites as a long-acting formulation for rhIFN.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.forename: Dengning
authors.initials: D
authors.lastname: Xia
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000648:ultrastructure*; D011817:Rabbits; D011994:Recombinant Proteins; D013696:Temperature; D015032:Zinc / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015032:Zinc